Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for resected melanoma.
Weber JS., Ascierto PA., Middleton MR., Hennicken D., Zoffoli R., Pieters A., Amadi A., Kupas K., Kotapati S., Moshyk A., Schadendorf D.
BACKGROUND: Nivolumab (an anti-programmed death-1 antibody) is an adjuvant standard of care for patients with high-risk resected melanoma, although a watch-and-wait strategy remains an option. In the absence of head-to-head evidence, an indirect treatment comparison (ITC) of adjuvant nivolumab versus placebo, the proxy for a watch-and-wait strategy, was conducted in patients with high-risk resected melanoma. METHODS: An ITC using the Bucher method compared nivolumab with placebo using intention-to-treat population data from the phase III CheckMate 238 (nivolumab vs ipilimumab; minimum follow-up, 4 years; NCT02388906) and European Organisation for Research and Treatment of Cancer (EORTC) 18071 (ipilimumab vs placebo; minimum follow-up, ≈4.5 years; NCT00636168) trials. The end-points were recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS). To account for cross-trial differences in staging and subsequent therapy, additional analyses examined patients with stage IIIB/IIIC disease and adjusted post-recurrence survival in EORTC 18071, respectively. RESULTS: Nivolumab versus placebo was associated with clinically meaningful improvements in RFS (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.42-0.68) and OS (HR, 0.63; 95% CI, 0.45-0.89). Nivolumab versus placebo was also associated with clinically meaningful improvements in RFS (HR, 0.53; 95% CI, 0.40-0.69), DMFS (HR, 0.62; 95% CI, 0.46-0.83) and OS (HR, 0.67; 95% CI, 0.47-0.97) in patients with stage IIIB/IIIC disease and in OS (HR, 0.65; 95% CI, 0.46-0.92) in the overall population after adjusting post-recurrence survival in EORTC 18071. CONCLUSION: This ITC shows that adjuvant nivolumab provides clinically meaningful improvements in RFS, DMFS and OS versus a watch-and-wait strategy in high-risk resected melanoma.